tbuckley/cabot-search huggingface dataset:
Diagnostic performance of natural language processing in detection of acute cancer VTE.
Authors: Naveen G. Subramanian, Hector Garcia Pleitez, Daniel Nguyen, Denai R. Milton, Jeff Jin, Elliana Young, Partow Kebriaei, Cristhiam Mauricio Rojas Hernandez
Journal: Journal of Clinical Oncology (2023)

e19062 Background: The annual incidence of venous thromboembolism (VTE) is roughly 50-fold increased post allogeneic hematopoietic cell transplant (HSCT). Timely detection of VTE events has a significant impact on morbidity and mortality from these events. Manual chart review is commonly used for detection of VTE events; however, this is labor intensive and often not feasible. The International Classification of Diseases, 10 th revision (ICD-10) has attempted to codify VTE more easily but has high false positive and false negative rates. Natural language processing (NLP) algorithms have been designed to improve detection of VTE events in electronic medical record systems over the past several years. This study aims to compare the accuracy of our institution’s NLP algorithm to the ICD-10 in detecting extremity VTE/pulmonary embolism (PE) events in hematopoietic stem cell transplant (HSCT) patients. Methods: This study was a retrospective analysis of adult patients who had allogeneic HSCT at MD Anderson between 2016-2020. Patient charts were assessed by three different methods for acute VTE events within 100 days of HSCT (index date). ICD-10 codes and our institution’s NLP algorithm were used separately to identify these VTE events. Afterwards, manual chart review was performed for confirmation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the ICD-10, NLP, and the NLP+ICD combination. Results: A total of 1,391 patient charts were analyzed in our study. There were 129 (9.3%) VTE events detected via manual chart review. Three methodologies were used for comparison: the NLP algorithm alone, the ICD code alone, and detection by NLP or ICD. The NLP algorithm alone had the best specificity (98.9%) and PPV (89.4%) of the three methods. The ICD-10 code had a statistically significant decrease in ability to detect acute VTE events compared to the NLP (p&lt;0.001) (Table). Of the 19 VTE events not identified by NLP, all were found in radiology or vascular laboratory reports. Conclusions: Our study shows the overall superior performance of the NLP algorithm, as it had higher sensitivity, specificity, PPV, and NPV compared to the ICD-10, as well as a better specificity and PPV compared to the combination of both methods. Future refinement of the NLP algorithm and combination with other detection methodologies will allow for more accurate detection of VTE in large cohorts. [Table: see text]
Comparing sentinel lymphadenectomy and complete lymphadenectomy among obese patients (BMI &gt;30) undergoing minimally invasive hysterectomy for early-stage endometrial cancer: An ACS-NSQIP database study.
Authors: Jessie Hollingsworth, Matthew Beier, Anusha Adkoli, Ruth Stephenson
Journal: Journal of Clinical Oncology (2023)

e17618 Background: In patients with endometrial cancer, lymph node assessment is used for staging and adjuvant treatment planning. Sentinel lymphadenectomy (SLN) is an acceptable alternative to complete lymphadenectomy due to decreased risk of major complications. As obesity increases in the United States, so does the rate of endometrial cancer. Complete staging may be more challenging in obese patients. Our goal was to evaluate the relative use and complication rates of sentinel versus complete lymphadenectomy among obese patients undergoing minimally invasive hysterectomy (MIH) for early-stage endometrial cancer. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients diagnosed with stage I to III endometrial carcinoma between 2015 and 2020 who underwent MIH, identified by Current Procedural Terminology (CPT) code. Extent of lymphadenectomy was also identified using CPT codes. Relative utilization of sentinel versus complete lymphadenectomy was evaluated over the study period. Propensity scores were used to control for potential confounders, and complication rates were compared between propensity matched cohorts of sentinel versus complete lymphadenectomy. Major and minor complications were defined by the Clavien-Dindo scale. Results: From 2015 to 2020 a total of 11,844 obese (BMI &gt; 30) patients underwent MIH for stage I to III endometrial cancer. Of these 7,067 (59%) had a lymph node assessment. Sentinel lymphadenectomy was completed in 3,845 patients, and complete lymphadenectomy was completed in 3,222 patients. Over the five-year period, the utilization of SLN increased for obese and non-obese patients. Prior to 2018, complete lymphadenectomy was performed more often. After 2018, SNL was more common. After propensity matching, there was no increased risk of death (OR 0.67, 95% CI 0.06-5.8, p = 1.0), infection (OR 0.86, 95% CI 0.69-1.1, p = 0.20), thrombo-embolic events (OR 0.77, 95% CI 0.51-1.1, p = 0.21), major complications (OR 0.84, 95% CI 0.66-1.1, p 0.15), or minor complications (OR 0.87, 95% CI 0.69-1.1, P = 0.22) in obese patients who underwent SLN compared to complete lymphadenectomy. Conclusions: The average BMI of patients who underwent MIH over the study period was 35. After controlling for comorbidities and other baseline characteristics, there were no significant differences in complication rates between sentinel and complete lymphadenectomy in obese patients. With the adoption of SLN, more patients may be adequately staged, providing more prognostic information and targeted therapies. These results suggest that sentinel lymphadenectomy is a technically feasible and safe staging procedure in obese patients.
Association of neutrophil to eosinophil ratio (NER) with clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line (1L) immune checkpoint inhibitors (ICI) –based regimens.
Authors: Marc Eid, Chris Labaki, Karl Semaan, Renee Maria Saliby, Eddy Saad, Valisha Shah, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

4557 Background: ICI-based regimens (ICI + ICI or ICI + VEGF targeted therapy [VEGF-TT]) represent current standard of care systemic therapies for the management of patients with mRCC. Robust biomarkers capable of predicting the therapeutic efficacy and safety of such regimens are still lacking. Eosinophils have been shown to play an important role in the response to immunotherapy. While recent investigations in RCC evaluated NER as a biomarker of poor response to immunotherapy, they did not fully account for the impact of different lines of therapy and the therapeutic classes of ICI-based regimens. We aimed to comprehensively evaluate the association of NER with clinical outcomes in patients with mRCC treated with 1L ICI regimens. Methods: We retrospectively reviewed data from patients with mRCC treated with first line ICI-based regimens (dual ICI or ICI + VEGF-TT) at Dana-Farber Cancer Institute. Clinicodemographic information was collected, including tumor histology, ECOG performance status, IMDC risk score. We examined NER at baseline and at 6, 12, and 24 weeks while patients were still receiving treatment. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) was a secondary endpoint. The association of NER with OS and TTF was evaluated using Cox regression models, adjusted for age, gender, BMI, histology, IMDC risk score and autoimmune disease. Results: Overall, 156 patients were included in the current analysis, with a median age of 61 years (IQR: 54-67). 60 patients received dual ICI therapy, while 96 were treated with ICI + VEGF-TT combinations. In the ICI+ICI group, a higher NER at baseline, 6 and 12 weeks was associated with worse OS. In the ICI + VEGF group, a higher NER only at 6 weeks appeared to be associated with worse OS. No association between NER and TTF was found. Conclusions: To our knowledge, this is the first study to investigate, across therapeutic classes, the association of NER with clinical outcomes in patients with mRCC treated with 1L ICI-based regimens. Higher NER was linked to poor survival outcomes, especially in patients receiving dual ICI therapy. Future translational studies are needed to clarify these findings. [Table: see text]
Long-term liver and renal dysfunction in patients with metastatic renal cell carcinoma treated with TKI monotherapy: COMPARZ study post-hoc analysis.
Authors: Aihetaimujiang Anwaier, Hailiang Zhang, Jiacui Yu, Hualin Wan, Su Miin Ong, Hao Zhe Tay, Ding-Wei Ye
Journal: Journal of Clinical Oncology (2023)

e16536 Background: Tyrosine kinase inhibitors (TKI) are currently the recommended treatment option for advanced renal cell carcinoma (aRCC) patient. Previous studies have shown some hepatorenal toxicity of TKI regimens, but differences in toxicity and long-term toxicity of TKIs have rarely been reported. This study aims to compare short- and long-term hepatorenal toxicity differences between pazopanib and sunitinib, and to explore the factors predisposing to hepatorenal toxicity. Methods: COMPARZ study was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in aRCC patients. Patients without liver metastasis and with available alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin results were enrolled to evaluate the effect of TKI on liver function. Patients with available serum creatinine (Cr), blood urea nitrogen (BUN), urine protein/creatinine ratio (UPC), and creatinine clearance (CrCl) were enrolled to evaluate factors associated with abnormal renal function. Lab indicators were compared between baseline and at months 12, 24, and 36 by paired t-test respectively. Linear mixed models were used to compare the difference in changes between treatment arms. Multivariate logistic regression was performed to examine the factors associated with recorded adverse events of hepatorenal toxicities. Results: Patients with abnormal liver function tests at baseline had higher elevated ALT, AST and total bilirubin levels at 12 months after TKIs treatment compared with patients who had normal baseline results. ALT levels were not significantly different between pazopanib arm and sunitinib arm at 12, 24 and 36 months. However, patients in the sunitinib arm had significantly higher AST levels than the pazopanib arm at 12 months (p = 0.049). There was no significant difference in total bilirubin level between pazopanib and sunitinib arm. Asian race and pazopanib were two factors that was significantly associated with increased risk of developing abnormal liver function. At 12 months, Cr levels were higher in the sunitinib arm compared with the pazopanib arm . BUN levels were lower in the pazopanib arm at 12 months but conversely was higher in the sunitinib arm at 24 months. UPC levels were significantly elevated in both treatment arms at 12 months (p &lt; 0.001) and 24 months (p = 0.008). CrCl levels decreased in both treatment arms, and was more obvious in the sunitinib group at 12 months and 24 months. Notably, male patients, Asian race, high BMI, and sunitinib were risk factors that were significantly associated with abnormal renal function. Conclusions: Compared with sunitinib, pazopanib was associated with a higher risk of hepatoxicity but lower risk of nephrotoxicity. Overall, Asian patients have a higher risk of developing abnormal liver and renal functions after TKI treatment.
Real-world (RW) treatment and surveillance patterns in patients with hepatocellular carcinoma (HCC) after resection (R) or ablation (A): Evidence from commercial and Medicare populations.
Authors: Amie Tan, Robert Schuldt, Sarika Ogale, Sairy Hernandez Painter
Journal: Journal of Clinical Oncology (2023)

e16223 Background: Prognosis of early HCC after curative resection (R) or ablation (A) remains poor due to lack of approved standard of care for adjuvant therapy. Guidelines recommend that patients (pt) receive surveillance imaging every 3 to 6 months for the first 2 years after R or A. RW data on treatment and surveillance patterns after curative intent therapy in the US can provide insights into how novel therapies may be integrated into the treatment paradigm. Methods: We conducted two retrospective, population-based studies of newly diagnosed HCC pts who underwent R or A as the first HCC therapy using data from Pharmetrics Plus commercial claims (2018 - 2021) and SEER-Medicare data (2010 - 2019), respectively. Continuous enrollment in health plans ≥6 months prior to diagnosis (Dx) date and ≥3 months after R or A, and no transplant during study period, was required. Treatments received within 3 months following R or A were defined as adjuvant therapy. Results: Among 705 eligible HCC pts with commercial insurance coverage, the majority were male (73%) and mean (SD) age at Dx was 61(9) years. Among them, 56% received A, 32% received R, and 12% had both R and A after Dx. 126/705 (18%) pts received adjuvant therapy. Most commonly used treatments were systemic therapy (44%) followed by transarterial chemoembolization (TACE) or transarterial embolization (TAE) (41%). Only 20% of pts received surveillance imaging in the first 2 years following R or A (Table). A total of 2,005 Medicare beneficiaries with HCC were identified from SEER-Medicare (male: 67%; White: 68%; Black: 11%; Asian: 19%). Mean (SD) age at Dx was 70(8) years. Among them, 54% received A, 36% received R, and 10% received both as the initial therapy for HCC. 238/2,005 (12%) pts received adjuvant therapy. Most commonly used treatments were TACE/TAE (61%) followed by systemic therapy (29%). Unlike the commercial insurance cohort, the majority of pts in the Medicare cohort (78%) received surveillance imaging within 2 years following R or A. Conclusions: Despite lack of clinical evidence and approved adjuvant therapy in the US, notable use of treatment in RW practice were observed. Types of adjuvant therapy used and utilization of surveillance varied by payers. A significant proportion of pts did not receive ongoing surveillance imaging despite guideline recommendations. These findings highlight the desire and unmet need for clinical evidence of treatments in pts with early HCC following curative intent therapy. [Table: see text]
Effect of GNA13 on the alteration of tumor microenvironmental components through exosomes to promote the development of head and neck tumors.
Authors: Weili Zhu, Miaoqing Zhao, Xiaoming Li, Yuting Ma, Zhi-Gang Yao, Kun Ru
Journal: Journal of Clinical Oncology (2023)

e18035 Background: Guanine nucleotide-binding protein alpha subunit 13 (GNA13) is closely related to tumor development, but the effect of GNA13 on the biological behavior of head and neck tumors is unknown. The aim of this study was to investigate whether GNA13 can influence the alteration of tumor microenvironment components through exosomes, which in turn promotes the development of head and neck squamous carcinoma (HNSCC). Methods: Using the Gene Expression Omnibus database, the differentially expressed gene GNA13 was screened. Immunohistochemistry and western blotting were used to detect the expression of GNA13 in HNSCC tissues and control tissues. GNA13 expression was down-regulated in tumor cell lines using transfection techniques. The effect of GNA13 downregulation on tumor cell growth was examined by in vitro experiments. RT-PCR and dual luciferase reporter gene assays were used to validate GNA13-regulated miRNAs and their target genes. Clonogenesis assays were used to examine the effect of target gene expression on fibroblasts, and the HNSCC xenograft mouse model was used to verify the role of GNA13 in tumor growth in vivo. The peripheral blood from patients with different stages of HNSCC was collected to determine the expression level of GNA13 in serum exosomes and to analyze its relationship with metastasis and postoperative recurrence. Results: GNA13 expression was elevated in HNSCC tissues and cells. The growth capacity of HNSCC cells was significantly reduced after downregulation of GNA13, which induced fibroblast conversion to MAF via exosomes and promoted their proliferation and migration. Meanwhile, GNA13 was able to regulate miR-26a-5p/STRADB expression in fibroblasts via exosomes. The overexpression of STRADB promoted the proliferation and migration of fibroblasts and induced their conversion to MAF. More importantly, in the conditioned medium of STRADB overexpressing fibroblasts, the proliferation and migration of HNSCC cells were promoted. Furthermore, knockdown of GNA13 expression inhibited the tumor growth in nude mice. It appeared that high expression of GNA13 in serum exosomes of patients with HNSCC was associated with poor prognosis. Conclusions: GNA13 regulates the miR-26a-5p/STRADB axis in fibroblasts via exosomes to create a metastasis-friendly microenvironment for tumor cells, ultimately promoting the progression of HNSCC. Meanwhile, the expression of GNA13 was positively correlated with the pathological grade and clinical stage of HNSCC, which seems to be a reliable indicator of tumor recurrence. Targeting this signaling pathway would be a promising therapeutic strategy for HNSCC.
Castration-resistant prostate cancer (CRPC) on PSMA-PET: Imaging features, disease distribution, and a comparison to castration-sensitive prostate cancer (CSPC).
Authors: Miles Hsu, Xinhe Shan, Rebecca Zhang, Austin Pantel, Samuel U Takvorian, Vivek Narayan, David J. Vaughn, Neha Vapiwala, Naomi B. Haas
Journal: Journal of Clinical Oncology (2023)

e17062 Background: 18 F-DCFPyL PET/CT is increasingly used in the staging and response assessment of patients (pts) with prostate cancer. Recent studies suggest that short-term ADT increases prostate-specific membrane antigen (PSMA) expression, whereas long-term ADT suppresses PSMA. Changes in PSMA expression after the development of CRPC are uncertain. We described 18 F-DCFPyL PET findings in pts with CRPC and compared them to findings in CSPC. Methods: We analyzed 538 18 F-DCFPyL scans performed at our large academic center. CRPC was defined as rising PSA w/ testosterone &lt; 50 ng/dL on ADT. M0 CRPC was defined as absence of extra-pelvic disease (dz) and oligometastatic CRPC (oCRPC) was defined as ≤ 5 LN + osseous lesions and absence of visceral dz. Highest SUV max (hSUVmax) was abstracted from radiologist impression. Means between groups were compared using two-tailed t-tests; undetectable PSA levels were scored as “0”. Logistic regression was used to compare dz distribution between castrate states. Significance was defined as p &lt; 0.05. Results: There were 81 pts with CRPC, 72 pts with metastatic CRPC (mCRPC) and 123 pts with mCSPC. The median ages of pts with mCRPC (74.5 years) and mCSPC (71) were similar. The mean PSAs of mCSPC (20.2 ng/mL) and mCRPC (69.4) were significantly different. hSUVmax was higher in mCRPC (mean 40.3, 95% CI 32.7 – 47.8) than in mHSPC (22.6, 18.4 – 26.9), p &lt; 0.001. Distribution of mCRPC lesions was as follows: prostate bed (26.4%), local pelvic LN (25%), distant LN (M1a, 41.7%), osseous (M1b, 16.7%), and visceral (M1c, 16.7%). In a multivariate analysis mCRPC pts had lower rates of pelvic LN dz and higher rates of M1c, with a trend toward increased M1b (p &lt; 0.10), compared to mCSPC pts. ADT and androgen pathway inhibition did not affect hSUVmax in CRPC. Within CRPC, there were 9 pts with M0 dz, 24 pts with oCRPC, and 48 pts with polymetastatic dz (pmCRPC). The ages (Table) of pmCRPC and oCRPC pts were similar. The mean PSA of pmCRPC (100.9) was higher than that of oCRPC (8.8) and M0 CRPC (5.7). hSUVmax between oCRPC (40.3) and pmCRPC (40.3) was similar. Conclusions: The greater hSUVmax in mCRPC may implicate the effect of ADT on PSMA expression or may describe differing tumor biology. mCRPC pts had less local dz and more frequent distant metastases, likely reflecting more advanced disease. These findings will help inform detection of developing castrate resistance on PSMA-PET. More data are needed on the classification of oligometastatic dz on PSMA-PET and the impact of hormone therapy on PSMA in CRPC. [Table: see text]
Outcomes among adult recipients of CD19 CAR T-cell therapy for Burkitt lymphoma.
Authors: Laura S. Samples, Hossein Sadrzadeh, Matthew J. Frigault, Caron Alyce Jacobson, Mehdi Hamadani, Ashwath Gurumurthi, Paolo Strati, Roni Shouval, Peter A. Riedell, Saurabh Dahiya, Jean Yared, Michael D. Jain, Frederick L. Locke, Lori Ann Leslie, Narendranath Epperla, Monalisa Ghosh, Alan Skarbnik, Brian T Hill, Manali K. Kamdar, Mazyar Shadman
Journal: Journal of Clinical Oncology (2023)

7571 Background: Burkitt lymphoma (BL) is a rare, but highly aggressive B-cell lymphoma associated with especially poor outcomes in patients with relapsed/refractory disease. Multiple CD19 chimeric antigen receptor (CAR) T-cell products have been FDA approved to treat relapsed/refractory B-cell non-Hodgkin lymphoma in the second-line setting, however little is known about CAR T-cell responses in patients with BL. This multicenter study aims to assess real-world outcomes among patients with BL treated with CAR T-cell therapy across the United States. Methods: This multicenter, retrospective chart review was conducted by abstracting data from the medical charts of patients with BL who received CAR T-cell therapy. Demographic characteristics were assessed along with pre-CAR treatments, bridging therapies, infusion-related complications, CAR-T responses, and the use of post-CAR systemic therapy and/or hematopoietic stem cell transplant. Results: A total of 13 patients with relapsed/refractory BL received CAR T-cell therapy after a median of 3 prior therapies (range 1-6). Most patients received axi-cel (n = 8), although tisa-cel (n = 3) and liso-cel (n = 2) were also represented. The median age of these patients was 38 (range 24-68). A total of 6 (46.2%) had evidence of central nervous system involvement at diagnosis and 5 (38.5%) had a prior history of autologous stem cell transplant. The overall response rate 1 month after infusion was 69.2% with a complete response rate of 53.8%. All patients experienced grade 1-2 cytokine release syndrome (CRS). No one experienced grade ≥3 CRS, but 2 patients developed grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS). Twenty-eight-day mortality was 23%, including one patient who died from grade 4 ICANS. Regarding long term data, only 4 (30.8%) patients sustained a complete response for more than 6 months. Median progression-free survival was 4.2 months (95% CI 28.2-257.6), and the 1-year overall survival rate was 61.5% (95% CI 0.56-0.67). Two (15.4%) patients received consolidative allogeneic stem cell transplants after CAR T-cell therapy, but both ultimately developed progressive disease. Conclusions: Relapsed/refractory BL is a rare and aggressive disease that remains challenging to treat despite the advent of CAR T-cell therapy. Further investigation is needed to determine the most effective management of these patients. We expect to include additional patients in this analysis over the coming months.